This project aims to continue investigation of a preclinical model of intestinal transplantation in inbred rats with the ultimate goal of making clinical intestinal transplantation a safe and effective treatment for short bowel syndrome in man. With the animal model we plan to determine if prolonged survival or tolerance of intestinal grafts can be produced without long term immunosuppression, by means of two new approaches to recipient pretreatment: enteral administration and portal vein injection of donor type cells combined with short-term cyclosporine. We plan to investigate if rejection of intestinal grafts can be detected before profound damage to graft or host has occurred, using three techniques: detecting the urinary excretion of low molecular weight polyethylene glycol which leaks from the rejecting bowel; measuring tissue levels of GI peptides and peptide receptors in the intestine; and measuring the expression of class II histocompatibility antigens on intestinal mucosa. Finally, we plan to investigate the mechanism of long-term tolerance of intestinal grafts by a variety of in vivo and in vitro techniques. These include adoptive transfer, mixed lymphocyte culture, and limiting dilution analysis cytotoxicity studies of lymphocytes obtained from tolerant hosts, and immunohistochemical staining. By these techniques we hope to determine the nature and time sequence of cellular and humoral responses which mediate tolerance of an intestinal allograft.